Endothelin, a potent vasoactive peptide, has just been discovered as the formerly described endothelial cell-derived contracting factor involved in the regulation of vascular tone. Although endothelin possesses potent vasoconstricter activity in vitro, its actions in vivo appear to be complex. In the systemic and renal vascular beds vasodilation seems to be the initial effect. In the pulmonary and vascular mesenteric circulatory regions endothelin causes an increase in resistance due to vasoconstriction. Endothelin also stimulates the growth of smooth muscle cells. An antagonist of endothelin will serve to characterize its receptor interaction and physiological effects. Analogues will be synthesized and tested for inhibition of endothelin actions on vascular conductance. A possible therapeutic for atherosclerosis, hypertension, as well as acute conditions of jury and shock may thus be developed.